ISSN:0953-8194    

DOI:10.1111/j.1365-2826.1995.tb00711.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

AbstractThe two major members of the family of natriuretic peptides (NPs) in brain, A‐type natriuretic peptide (ANP) and C‐type natriuretic peptide (CNP) exert opposing actions on the neuroendocrine regulation of prolactin (PRL) secretion. We have targeted for compromise and destruction cells within the diencephalon which bear receptors for ANP (NPR‐A receptors), CNP (NPR‐B receptors), or both peptides (NPR‐C receptors) using novel cytotoxin cell targeting methodology in order to determine if the neuroendocrine effects of these two peptides are exerted on similar cell systems. In animals pretreated with ANP conjugated to the cytotoxic A chain of ricin, central administration of a dose of ANP which is known to inhibit PRL secretion did not alter PRL levels in plasma; however, subsequent administration of CNP elicited the stimulation of PRL secretion. In rats pretreated with CNP‐ricin A chain conjugate, a treatment we hypothesize targets for destruction CNP responsive cells, ANP injection did inhibit PRL secretion, while the stimulatory effect of CNP was absent. These results suggest that the neuroendocrine effects of these two natriuretic peptides on PRL secretion are expressed on different cellular elements of the hypothalamo‐pituitary axis. Furthermore, they reveal that neither peptide acts directly on the tuberoinfundibular dopamine system since pretreatment with either cytotoxin conjugate failed to alter basal PRL levels. Thus ANP and CNP do not appear to express opposing actions on the same cell systems, suggesting the recruitment of each peptide individually by differing, unique stimuli fo

ISSN:0953-8194    

DOI:10.1111/j.1365-2826.1995.tb00712.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

AbstractEndocrine side effects of the immunosuppressive drug cyclosporine (CyA) include changes in anterior pituitary hormone secretion. The aim of the present study was to examine the effects of CyA on the responsiveness ofin situand ectopic anterior pituitary prolactin (PRL), growth hormone (GH) and luteinizing hormone (LH) release response to dopamine (DA) and thyrotropin‐releasing hormone (TRH) treatment in young female rats, and to evaluate the possible PRL participation in these effects. Thirty day old rats were rendered hyperprolactinemic by transplanting an anterior pituitary gland of a littermate donor, under the kidney capsule, and were then injected with CyA or vehicle for 2 or 8 days. Sham‐operated rats were used as controls and treated in the same way. CyA treatment prevented the increase in plasma PRL levels which occurred in controls after pituitary grafting.In vitrobasal PRL release ofin situpituitaries from either sham‐operated and/or pituitary‐grafted animals was decreased by CyA treatment at any point studied. Basalin vitrosecretion of GH was only decreased in thein situpituitaries from grafted animals after 2 days of CyA therapy. The presence of an ectopic pituitary lead to an increase in thein vitrobasal LH secretion fromin situpituitaries as compared to those from sham‐operated rats. Basal LH release rates were not changed by CyA treatment, although the LH releasein vitrodid increase in the in situ pituitaries from sham‐operated animals treated with the drug for 2 days.DA addition to the incubation media decreased thein vitrorelease of PRL, GH and LH from thein situpituitaries of sham‐operated and pituitary‐grafted animals treated with vehicle. In CyA treated animals, DA decreasedin vitroPRL release from thein situpituitaries of animals, independently of the presence or absence of an ectopic pituitary. Reductions of thein vitroGH and LH release after DA treatment were higher in thein situpituitaries from grafted animals on day 8 of CyA or vehicle treatment.TRH increased thein vitrorelease of the three hormones with differential effects related to the length of the treatment with CyA and/or the presence of an ectopic pituitary.In vitrorelease of PRL and GH by ectopic pituitaries was inhibited by previous treatment with CyA and this effect was decreased proportional to the duration of the treatment with the drug, while LH secretion was not modified. Addition of DA to the incubation media resulted in a marked reduction ofin vitroPRL and GH release, but only at day 8 of vehicle treatment on GH release did DA addition to media further decrease the release of both hormones from ectopic pituitaries from animals treated for 2 or 8 days with the drug, whereas LH secretion was not modified. TRH addition to the incubation media of ectopic pituitaries surprisingly reduced PRL and GH secretion on day 8 of CyA treatment or after surgery. The results of these studies suggest that CyA can act directly at the hypophyseal level modifying pituitary responsiveness to external stimuli. CyA seems to exert its main effects on lactotroph activity while its effects on somatotrophs and gonado

ISSN:0953-8194    

DOI:10.1111/j.1365-2826.1995.tb00713.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

AbstractDouble stainingin situhybridization studies have shown that angiotensin II (All) type 1 receptors (AT1) in the hypothalamic paraventricular nucleus (PVN) are located primarily in corticotropin releasing hormone (CRH) neurons of the parvicellular subdivision. The purpose of these studies was to investigate the role of All regulating the hypothalamic‐pituitary adrenal (HPA) axis, by correlating AT1receptor expression levels in the PVN with the known changes in activity of the HPA axis under different stress paradigms, and manipulation of circulating glucocorticoids. AT1receptor mRNA was measured by in situ hybridization using35S‐labelled cRNA probes and All binding by autoradiography using125I[Sar1,lle8]All in slide mounted hypothalamic sections. AT1receptor mRNA levels and All binding in the PVN were reduced by about 20% 18 h after adrenalectomy remaining at these levels up to 6 days after. This effect was prevented by corticosterone administration in the drinking water, or dexamethasone injection (100 mg, s.c., daily). Conversely, dexamethasone injection in intact rats caused a 20% increase in AT1receptor mRNA in the PVN. AT1receptor mRNA and binding in the PVN increased 4 h after exposure to stress paradigms associated with activation of the HPA axis (immobilization for 1 h, or i.p. injection of 1.5 M NaCl), and remained elevated after repeated daily stress for 14 days. Unexpectedly, two osmotic stress models associated with inhibition of the HPA axis (60 h water deprivation or 12 days of 2% saline intake) also resulted in increased AT1receptor mRNA levels and All binding in the parvicellular PVN. In intact rats, the stimulatory effect of acute stress on AT1receptor mRNA in the PVN was significantly enhanced by dexamethasone administration (100 μg, s.c., 14 h and 1 h prior to stress), while in adrenalectomized rats, with or without glucocorticoid replacement, stress reduced rather than increased, AT1receptor mRNA. Dexamethasone, 100 μg, injected sc within 1 min the beginning of immobilization in adrenalectomized rats, increased AT1receptor mRNA in the PVN to levels significantly higher than those after dexamethasone alone, indicating that the stress induced glucocorticoid surge is required for the stimulatory effect of stress on AT1receptor mRNA. The data suggest that AT1receptor expression in the PVN is under dual control during stress: stress‐activated inhibitory pathways and the stimulatory effect of glucocorticoids. The lack of specificity of the changes in AT1receptor expression in the PVN following stressors with opposite effects on ACTH secretion (osmotic and physical‐psychological stress) does not support a role for All as a major determinant of the response of the HPA axis duri

ISSN:0953-8194    

DOI:10.1111/j.1365-2826.1995.tb00714.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

AbstractWe have employed the GH3rat pituitary cell line to investigate whether nicotine can regulate prolactin (PRL) gene expression. Nicotine strongly inhibited (45%) transient expression of a construct containing the first 187 base‐pairs of the rat PRL promoter cloned upstream of the chloramphenicol acetyl transferase (CAT) gene. This implies that nicotine acts directly on the GH3cells to inhibit transcription directed by the PRL promoter. Expression of a control reporter construct containing the CAT gene under the control of the RSV promoter was not affected by exposure of the cells to nicotine, demonstrating that the effect of nicotine is promoter‐specific. The inhibition by nicotine of PRL promoter activity was not blocked by hexamethonium, suggesting that this effect of nicotine may be mediated by a novel type of nicotine receptor previously described in frog pituitary cells. Nicotine was also observed to yield a concentration‐dependent inhibition of the stimulation by thyrotrophin‐releasing hormone (TRH) of PRL promoter activity, implying that nicotine can also interfere with hormonal regulation of the PRL gene. These results suggest that the reduced serum PRL levels that result from smoking may originate in part from decreased transcription of the PRL gene resulting from a direct effect of nicotine on pituitary PRL‐secret

ISSN:0953-8194    

DOI:10.1111/j.1365-2826.1995.tb00715.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

AbstractIn the present study the regions of the brain showing an increase in the number of FOS protein stained cells 180 min following intravenous saline or bacterial lipopolysaccharide (LPS) treatment were investigated and correlated with changes in body temperature and plasma corticosterone levels. Particular attention was given to the possible involvement of the circumventricular organs and regions of the brainstem containing central noradrenergic neurones. LPS at doses of 0.35, 3.5 and 50 μg caused highly significant increases in FOS protein expression in the organum vasculosum of lamina terminalis, the area postrema and the subfornical organ compared with saline controls. Marked increases in bacterial lipopolysaccharide‐induced FOS protein expression were observed in the ventrolateral medulla, the nucleus of the solitary tract and the locus coeruleus which contain the A1, A2 and A6 noradrenergic neurones respectively. The changes in body temperature induced by LPS were found to be dependent upon the dose of LPS administered; the lowest dose employed (0.35 μg) induced an immediate and sustained fever, 3.5 μg LPS caused a biphasic response consisting of a hypothermic response followed by a febrile response, whereas 50 μg LPS induced a hypothermic response which then normalised by 160 min post‐injection. Intravenous saline injection had no significant effect on body temperature. The occurance of LPS‐induced hypothermia was coincident with increased FOS expression in the bed nucleus of stria terminalis, which houses vasopressinergic neurones involved in antipyresis, whereas in animals showing an LPS‐induced febrile response there was no significant difference in the number of FOS stained cells in the bed nucleus of stria terminalis compared with saline treated animals. LPS also caused marked increases in FOS protein expression in the parvocellular regions of the paraventricular nucleus (pPVN) of the hypothalamus, the central nucleus of the amygdala and the ventral septa1 area. Plasma corticosterone was unaffected by the lowest dose of LPS (0.35 μg), however the higher doses employed (3.5 and 50 μg) caused significant increases in plasma corticosterone which correlated with the increases in the number of FOS stained cells in the pPVN. The results of the present study suggest that, in addition to the organum vasculosum of lamina terminalis, the area postrema and subfornical organ may be important in the responses to antigenic challenge that are mediated by the central nervous system. They also add support to the possible involvement of the bed nucleus of stria terminalis in LPS‐induced hypothermia and of the involvement of the of the major noradrenergic cell groups (A1, A2&A6) and a number of hypothalamic and extrahypothalamic forebrain regions in the interaction of immune and central

ISSN:0953-8194    

DOI:10.1111/j.1365-2826.1995.tb00716.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

AbstractThe mechanisms involved in 2‐deoxy‐D‐glucose (2‐DG)‐induced growth hormone (GH) suppression in the rat were examined. Conscious male rats were given 2‐DG by intracerebroventricular (icv) injection and the pulsatile GH secretion was monitored for 6 h. The single icv injection of 2‐DG (8 mg/rat) eliminated pulsatile GH secretion in conscious rats. Pretreatment with somatostatin (SS) antiserum completely restored the suppressed GH secretion in the 2‐DG treated rats. Hypothalamic GH‐releasing hormone (GRH) and SS mRNA levels were not altered by single and multiple icv injections of 2‐DG. These findings suggest that 2‐DG‐induced GH suppression is primarily due to hypersecretion of SS without a significant change at the transcr

ISSN:0953-8194    

DOI:10.1111/j.1365-2826.1995.tb00717.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

AbstractThe aim of this study was to determine the terminal products of processing of the N‐terminal part of proopiomelanocortin (POMC) in pituitary melanotrope cells ofXenopus laevis.Biosyntheticin vitrolabelling studies showed that POMC is rapidly processed to form N‐terminal peptides with an estimated molecular mass of 18 kDa, 9 kDa and 4 kDa. All peptides were released into the medium, indicating that they are processing end products. An antiserum was raised against the synthetic N‐terminal eight amino acids of the putativeXenopusγ‐MSH which is present in the N‐terminal part of POMC. With immunocytochemistry we demonstrated that γ‐MSH‐immunoreactive material in the pituitary gland is restricted to the pars intermedia. A radioimmunoassay in combination with reversed‐phase HPLC revealed the presence of at least two γ‐MSH‐like peptides. Complete purification followed by electrospray ionization mass spectrometry and amino acid sequence determination showed that these peptides are γ1‐MSH and glycosylated γ3‐MSH. The amounts of these γ‐MSH peptides were low compared to the other POMC‐derived peptides, α‐MSH and β‐endorphin. Only 10% of POMC is processed into γ‐MSH peptides and the 4 kDa peptide, leaving the 18 kDa an

ISSN:0953-8194    

DOI:10.1111/j.1365-2826.1995.tb00718.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

ISSN:0953-8194    

DOI:10.1111/j.1365-2826.1995.tb00719.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY